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Cellular alchemy turns skin cells into brain cells

By Clare Wilson

Move over stem cells. A different kind of cellular alchemy is allowing cells to be converted directly into other tissues to treat disease or mend injuries.

Stem cells have long been touted as the future of regenerative medicine as they can multiply indefinitely and be turned into many different cell types. Ideally, this would take a personal approach – a patient’s own cells would be converted into whatever type of cell is required to fix their injury or treat their symptoms. Earlier this year, for instance, people with age-related macular degeneration, the most common cause of blindness in the West, had retinal cells made from their own stem cells injected into their eyes.

Mature cells can be converted into stem cells by exposing them to a cocktail of chemicals that reverts them back to an embryonic-like state. Another set of chemicals is then used to turn the cells into the desired tissue type.

Skipping the stem cell stage would be more efficient, says Andrew Yoo of Washington University in St Louis, Missouri, and would reduce the chance that the new tissue could grow into a tumour – a risk with stem cells because of their capacity to regenerate.

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Just add chemicals

Yoo has now managed to do just that, using a process known as “transdifferentiation”. His team have turned human skin cells into medium spiny neurons, the cells that go wrong in Huntington’s disease.

To the skin cells, the team added two short snippets of genetic material called microRNAs. MicroRNAs are signalling molecules and the two they picked turn on genes in brain cells during embryonic development. They also added four transcription factors – another kind of signalling molecule – to turn on genes normally active in medium spiny neurons.

Within four weeks the skin cells had changed into MSNs. When put into the brains of mice, the cells survived for at least six months and made connections with the native tissue. “This is a very cool result,” says Ronald McKay of the Lieber Institute for Brain Development in Baltimore.

The team’s next step is to transplant the cells into mice with a version of Huntington’s to see if the new neurons reduce their symptoms.

Cocktail of cells

“Being able to produce cells with medium spiny neuron characteristics directly without first having to generate stem cells is impressive,” says Edward Wild of University College London. “Using this offers the tantalising prospect of cell replacement treatments.”

Wild points out, however, that before this approach can be used on people with Huntington’s, researchers would first have to correct the faulty genetic mutation in their skin cells. And while medium spiny neurons are the first to degenerate in the disease, other brain cells may also be affected. “When it comes to cell replacement we should probably be aiming for a cocktail of cells,” says Wild.

A few examples of transdifferentiation have previously been reported, including the creation of heart and pancreas cells.